2.22.2008

Statins Updated

A poster posited a link between Parkinson's Disease (PD) and Statin use, which led me to an article in Movement Disorders, 2006 (PubMed ID 17177184) that points out, in a retrospective study, a strong link between low LDL and Parkinson's incidence. The lower the LDL, the more people had PD: up to 3 times as often with an LDL below 93.

However, that same article seemed to find a 'neuroprotective' effect for statins. The poster obviously knew more biochemistry than me, so I'm not incredulous, that's just what I found in an admittedly quick search. Updated articles are welcome. It certainly did confirm a link between low LDL and Parkinson's, from which I can infer that LDL is perhaps not entirely deserving of the pejorative 'bad' cholesterol label.

A Google search on statins, however, on the broader issue of Number Needed to Treat analysis, showed very high NNTs, like 33 here, based on a 2003 Lancet article. I'm not sure how reliable that is. However, with an NNT of 33 in people with diabetes, I suppose there is good reason to question statin use given the lack of mortality benefit, and given the serious side-effects; I'm not sure about PD, but pancreatitis and rhabdomyolysis are no picnic.

Just don't ask what the NNT is for epinephrine in out-of-hospital resuscitation. The evidence for a lot of our critical situation algorithms seems a bit thin from podcasts I listen to. Just a tad bit hard to study.
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2 comments:

Anonymous said...

Predictably, initial use of statins should be of benefit in any disease that includes an inflammatory process--as most all the neurodegenerative diseases are theorized to include. Statins are powerful anti-inflammatory agents, and initially should decrease this aspect of any disease. These agents effectively increase perfusion everywhere, also , so with initial use, any disease that includes vascular problems should improve. With continued use, the other "pleiotrophic" effects become evident: these pleiotrophic effects are mainly the result of depression in isoprenoid biosynthesis leading to impairment of the production of a variety of metabolic substrates such as dolichols, crucial for N-linked glycosylation; geranylgeranyl pyrophosphate, necessary for coenzyme Q10; farnesyl-pyrophosphate, necessary for the maturation of prelamin A and B-type lamins and G-proteins ;and isopentenylpyrophosphate, involved in direct modification of selenocysteinyl-tRNA and thus indirectly related to the synthesis of all selenoproteins (last estimated at 35). (glutathione reductase is depleted by statins--this substance is responsible for recycling glutathione in the brain)
Important to remember: brain cholesterol has a half-life of ~5yrs. Fat soluble statins, Lipitor, zocor, crestor, all cross the blood brain barrier and thus are able to affect the level of brain cholesterol. If a critical level of cholesterol exists for the brain, more time than a 2 to 3 yr period normally used in clinical trials would be necessary to appreciate the effects of lowering cholesterol levels in the brain.
Following article may also be important when considering effect of statins upon cognitive function and/or neurodegenerative diseases:
Barres and Smith's in vitro findings of importance of brain cholesterol (recalling that fat soluble statins cross the blood brain barrier) :
www.tinyurl.com/2bsnta
Neurons need cholesterol secreted by glial cells to form and maintain functional neuronal synapses. In addition to synaptogenesis, cholesterol is probably responsible for production and transport of vesicles necessary for neurotransmission. If one ascribes to the theory of brain plasticity, then deliberately suppressing cholesterol metabolism within the brain seems questionable to me.....

February 23, 2008 at 2:26 PM
Tyro said...

This is a good critique of most, if not all, trials that we use to validate our new drugs. Often the time period is too short to fully evaluate effects, which I would bet leads to the later drop in use for many drugs (think Vioxx).

CoQ10 is also a mainstay of complementary medicine supplements, so I could see how reducing levels might lead to bad side effects. Your arguments are compelling, I must say.

Going into emergency medicine, I probably won't be starting any drugs intended to stay around for many years, but I'll certainly look at statins with a more critical eye.

February 24, 2008 at 7:30 AM

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